Mycobacterium tuberculosis is the bacillus which causes tuberculosis in humans. Tuberculosis affects about 2 billion people—about one third of the world's population, according to WHO estimates. This bacillus can lie latent within the host, often for several decades, until the disease gets triggered. A mycobacterial infection often manifests itself when the carrier is immunocompromised, either by nutritional deficiency or the acquired immunodeficiency syndrome (AIDS). The transcriptional machinery is of particular importance in this organism as it has only one ribosomal RNA operon, making efficient transcription necessary for the survival and pathogenicity of this organism. This aspect makes the transcription machinery an attractive target for drug-design. Indeed, a key component of tuberculosis therapy is rifampicin, an RNA polymerase inhibitor.
The central enzyme of bacterial gene expression, the DNA-dependent RNA polymerase, consists of five sub-units. The two α subunits along with the β and β′ subunits form a stable catalytic unit that is involved in RNA elongation. The fifth subunit of RNA polymerase is the sigma factor (σ) that provides the RNA polymerase with promoter recognition features and is necessary for the initiation of transcription. M. tuberculosis has at least 13 sigma (σ) factors: 3 primary sigma factors, 10 extra-cytoplasmic function (ECF) sigma factors and one alternative sigma factor, pvdS. The interplay between signal transduction and the transcriptional regulatory mechanisms allows the bacillus to respond to changes in the environment by synthesizing new proteins or down-regulating others. This ability is key to the bacillus's adaptability to survive the stresses inside the host until a failure in host defenses leads to a reactivation of the disease.